Tubular Handling of Phosphate along the Nephron of Thyroparathyroidectomized Rats Injected with Ethane-1-Hydroxy-1,1-Diphosphonate

1981 ◽  
Vol 60 (2) ◽  
pp. 171-177 ◽  
Author(s):  
R. C. Mühlbauer ◽  
J.-P. Bonjour ◽  
H. Fleisch
Keyword(s):  
Proximal Tubule ◽  
Bone Mineral ◽  
Adaptive Response ◽  
Distal Tubule ◽  
Tubular Reabsorption ◽  
Free Flow ◽  
Induced Changes ◽  
Terminal Nephron ◽  
Early Proximal Tubule

1. Previous studies have shown that in thyroparathyroidectomized rats injection of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at doses that inhibit bone mineral retention (0.16 mmol = 10 mg of phosphorus/kg body wt. per day subcutaneously) leads to a decrease in the net tubular reabsorption of phosphate. 2. In the present work the tubular response to EHDP (0.16 mmol/kg body wt.) injected subcutaneously for 9 days has been localized by free-flow micropuncture in thyroparathyroidectomized rats. 3. The results show that the net tubular reabsorption of phosphate along the first portion of the (early) proximal tubule was markedly depressed in the EHDP-injected thyroparathyroidectomized rats compared with that in the pair-fed thyroparathyroidectomized control animals. In this latter group the delivery of phosphate to the distal tubule was larger than in the final urine, confirming previous reports. In the EHDP-injected thyroparathyroidectomized rats no difference in delivery of phosphate was found between the distal tubule and the final urine, suggesting that diphosphonate inhibited net reabsorption of phosphate in the terminal nephron. 4. The sites of the EHDP-induced changes in the tubular handling of phosphate were similar to those previously determined for the adaptive response to an increase in the supply of phosphate.

Secretion of Inorganic Phosphate in the Rat Nephron

1975 ◽  
Vol 48 (6) ◽  
pp. 475-489 ◽  
Author(s):  
J.-F. Boudry ◽  
U. Troehler ◽  
M. Touabi ◽  
H. Fleisch ◽  
J.-P. Bonjour
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Inorganic Phosphate ◽  
Specific Radioactivity ◽  
Distal Tubule ◽  
High Plasma ◽  
Tubular Secretion ◽  
Tubular Reabsorption ◽  
Anaesthetized Rats ◽  
Terminal Nephron

1. The existence of tubular secretion of inorganic phosphate (Pi) in the mammalian kidney has been investigated by studying the renal response of rats infused with sodium phosphate by three different techniques. 2. Clearance studies indicate that, in anaesthetized rats, the net tubular reabsorption decreases markedly in response to Pi infusion. In conscious rats, the clearance of Pi slightly exceeded that of inulin at high plasma Pi concentration. 3. Free-flow micropuncture in control rats showed a net tubular reabsorption of Pi along the proximal tubule, and probably between the end of the distal tubule and the ureteral urine. In phosphate-loaded rats, whether receiving parathyroid hormone or not, an apparent net secretion of Pi was observed between the end of the distal tubule and the ureteral urine. In the phosphate-loaded group receiving parathyroid hormone, net secretion was also observed very early in the proximal tubule followed by a predominant reabsorption along this segment. Thus the early proximal tubule and probably also the terminal nephron can be the site of either net reabsorption or net secretion. 4. Microperfusions of proximal tubules show a fall in the specific radioactivity of the perfused radioactive Pi solution, indicating entry of Pi into the lumen.

scholarly journals Effect of propranolol on phosphate reabsorption by superficial nephron segments in response to parathyroid hormone in phosphate-deprived rats.

1990 ◽  
Vol 1 (2) ◽  
pp. 200-204
Author(s):  
A Rybczynska ◽  
A Hoppe ◽  
F G Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Free Flow ◽  
Phosphate Deprivation ◽  
Phosphate Reabsorption ◽  
Nephron Segments ◽  
Pars Recta

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone. The decreased phosphaturic response to parathyroid hormone in rats fed a low phosphate diet for 1 day can be restored by propranolol infusion. Free-flow micropuncture studies were performed to localize the nephron site of restoration of the phosphaturic effect of parathyroid hormone by propranolol in rats deprived of phosphate for one day. In animals fed low phosphate diet and in the presence of parathyroid hormone, propranolol infusion did not change phosphate delivery to the late proximal tubule; however, fractional delivery of phosphate to the early distal tubule was significantly increased from 18.3 +/- 2.9 to 32.2 +/- 4.1%. In rats fed a normal phosphate diet, propranolol infusion did not change phosphate delivery along the nephron. We conclude that the restoration of the phosphaturic effect of parathyroid hormone by propranolol infusion in rats deprived of phosphate for 1 day is primarily due to decreased reabsorption of phosphate by superficial loop segments, most likely the pars recta segment of the proximal tubule.

Nephron sites of action of nicotinamide on phosphate reabsorption

1984 ◽  
Vol 246 (1) ◽  
pp. F27-F31
Author(s):  
J. A. Haas ◽  
T. J. Berndt ◽  
A. Haramati ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Proximal Convoluted Tubule ◽  
Free Flow ◽  
Loop Of Henle ◽  
Phosphate Deprivation ◽  
Phosphate Reabsorption ◽  
Pars Recta ◽  
Sites Of Action

The administration of nicotinamide results in urinary phosphate excretions similar to those obtained with pharmacologic doses of parathyroid hormone (PTH). Free-flow micropuncture was performed to localize the nephron site(s) of inhibition of phosphate reabsorption by nicotinamide or PTH in thyroparathyroidectomized (TPTX) rats stabilized on a normal or low phosphate diet. In rats fed a normal phosphate diet phosphaturia was observed following either nicotinamide or PTH treatment. Nicotinamide inhibited phosphate reabsorption in the loop of Henle (pars recta) but not in the accessible proximal tubule. PTH inhibited phosphate reabsorption in both the accessible proximal tubule and the pars recta. In phosphate deprivation, the phosphaturic response to either nicotinamide or PTH was blunted. Although phosphate reabsorption was markedly inhibited in the accessible proximal tubule with both nicotinamide and PTH, subsequent reabsorption in the loop of Henle and distal tubule blunted the phosphaturia. We conclude that nicotinamide primarily inhibits phosphate reabsorption by the pars recta in rats fed a normal phosphate diet, whereas it inhibits phosphate reabsorption by the proximal convoluted tubule in rats fed a low phosphate diet. Furthermore, avid reabsorption of phosphate in the pars recta accounts for the resistance to the phosphaturic effect of nicotinamide or PTH seen in rats fed a low phosphate diet.

Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism

1990 ◽  
Vol 123 (2) ◽  
pp. 194-202 ◽  
Author(s):  
Jan H. Kristiansen ◽  
Jens Brøchner-Mortensen ◽  
Kaj O. Pedersen ◽  
Søren Jensen ◽  
Torben Glud
Keyword(s):  
Primary Hyperparathyroidism ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Tubular Reabsorption ◽  
Positive Linear Correlation ◽  
Calcium Reabsorption ◽  
Renal Tubular Reabsorption ◽  
The Absolute ◽  
Renal Tubular ◽  
Reabsorption Rate

Abstract. Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 ageand sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calsium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.

Effects of Low-dose Angiotensin II Infusion on Loop Segment Reabsorption: A Free-Flow Micropuncture Study in Rats

1995 ◽  
Vol 88 (3) ◽  
pp. 351-358 ◽  
Author(s):  
René Fransen ◽  
Walther H. Boer ◽  
Remmert De Roos ◽  
Peter Boer ◽  
Hein A. Koomans
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Low Dose ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Free Flow ◽  
Control Group ◽  
Aortic Constriction ◽  
Micropuncture Study ◽  
Reabsorption Rate

1. Little direct information is available on the actions of angiotensin II beyond the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and the early distal tubule. 2. Endogenous angiotensin II was suppressed by pretreament with enalapril. Compared with a control group, angiotensin II increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased from 1.32 ± 0.05 to 1.10 ± 0.05 ml/min, Na+ excretion from 0.43 ± 0.09 to 0.13 ± 0.03 μmol/min, fractional delivery of water at the late proximal tubule from 50.1 ± 1.7 to 42.9 ± 3.2%, fractional delivery of Na+ at the late proximal tubule from 46.5 ± 1.3 to 39.1 ± 3.5% and fractional delivery of water at the early distal tubule from 26.4 ± 1.4 to 21.9 ± 1.0% (P < 0.05 for each variable). Fractional delivery of Na+ at the early distal tubule did not change significantly. 3. Similar experiments were performed during partial aortic constriction to exclude the effects of increased perfusion pressure. The data obtained were similar, except that in this group the fractional delivery of Na+ at the early distal tubule decreased from 8.6 ± 0.7 to 6.8 ± 0.9% (P < 0.05). 4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption between late proximal and early distal tubule was not disturbed by angiotensin II. For water, however, this relation tended to shift to a higher reabsorption rate. 5. The decrease in fractional excretion of Li+ followed the decrease in proximal reabsorption as measured directly by micropuncture. Angiotensin II infusion did not appear to affect Li+ reabsorption beyond the proximal tubule. Distal fractional Na+ reabsorption estimated by the Li+ clearance increased significantly during angiotensin II infusion. 6. In conclusion, our data indicate that a Na+-retaining dose of angiotensin II increases Na+ reabsorption in the proximal tubule, an effect correctly indicated by the change in the fractional excretion of Li+, does not influence Na+ reabsorption in the loop of Henle beyond the proximal tubule, but may increase Na+ reabsorption in more distal segments.

Distal perfusion studies: transport stimulation by native tubule fluid

1990 ◽  
Vol 258 (6) ◽  
pp. F1523-F1527 ◽  
Author(s):  
G. Malnic ◽  
R. W. Berliner ◽  
G. Giebisch
Keyword(s):  
Proximal Tubule ◽  
Distal Tubule ◽  
Free Flow ◽  
Flow Conditions ◽  
Perfusion Studies ◽  
Potassium Secretion ◽  
Series Of Experiments ◽  
Distal Tubules ◽  
Distal Perfusion ◽  
Tubule Fluid

It is well established that potassium secretion into the distal tubule increases with the rate of flow. In a previous study [G. Malnic, R. W. Berliner, and G. Giebisch. Am. J. Physiol. 256 (Renal Fluid Electrolyte Physiol. 25): F932-F1271, 1989] we found that the increase with the rate of perfusion with a fluid made up to resemble that normally found in the early distal tubule was substantially less than the increase in free-flow conditions [R. N. Khuri, M. Wiederholt, N. Strieder, and G. Giebisch. Am. J. Physiol. 228: 1249–1261, 1975]. Because of the possibility that some important component was missing from the artificial fluid, we have carried out another series of experiments in which distal tubules were perfused with fluid collected from late proximal tubules and compared the results with those obtained when tubules were perfused with an artificial fluid with an electrolyte composition similar to that of late proximal fluid. When proximal tubule fluid was used, the potassium concentrations in the collected distal fluid were higher and better maintained with increasing flow than when the artificial fluid was used, and consequently the rate of potassium secretion was substantially greater with the proximal tubule fluid, approaching the results of previous studies in free flow. The nature of the component missing from the artificial solution is not known.

Inhibition of urate excretion by pyrazinoate: a micropuncture study

1975 ◽  
Vol 229 (6) ◽  
pp. 1604-1608 ◽  
Author(s):  
F Roch-Ramel ◽  
IM Weiner
Keyword(s):  
Proximal Tubule ◽  
Renal Clearance ◽  
Left Kidney ◽  
Distal Tubule ◽  
Major Effect ◽  
The Other ◽  
Free Flow ◽  
Clearance Ratio ◽  
Cebus Albifrons ◽  
Micropuncture Study

Anesthetized monkeys (Cebus albifrons) undergoing moderate mannitol diuresis were treated with infusions containing lithium urate to elevate the urate concentration in plasma to 45-68 mug/ml and containing the uricosuric drug, 2-nitroprobenecid, to enhance the renal clearance or urate. The urate/inulin clearance ratio was 0.55 +/- 0.03. When pyrazinoate was added to the infusion the clearance ratio fell to 0.26 +/- 0.02. Analysis of free-flow micropuncture samples revealed a major effect of pyrazinoate in the proximal tubule, although an additional, smaller action in the distal tubule could not be definitely excluded. When droplets containing [14C]urate and [3H]inulin were streaked on the surface of the left kidney more urate than inulin appeared in the urine from that kidney (but not the other) within the first 3 min after application. This "excess" excretion of urate could be largely eliminated by pretreatment with pyrazinoate. The results suggest that pyrazinoate inhibits secretion of urate in the proximal tubule.

Electrolyte handling by the superficial nephron of the rabbit

1986 ◽  
Vol 250 (4) ◽  
pp. F590-F595 ◽  
Author(s):  
N. L. Wong ◽  
S. J. Whiting ◽  
C. L. Mizgala ◽  
G. A. Quamme
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Concentration Ratio ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Mean Value ◽  
Loop Of Henle ◽  
Collection Site ◽  
Micropuncture Study ◽  
The Mean

A micropuncture study of the rabbit was performed to evaluate the function of the superficial nephron. The mean glomerular filtration rate of the left micropunctured kidney was 4.0 +/- 0.8 ml/min. The concentration profile of electrolytes within the proximal tubule was similar to that of species previously investigated except for potassium. The mean tubular fluid (TF)-ultrafilterable (UF) concentration ratios were as follows: sodium, 1.01 +/- 0.03; chloride, 1.14 +/- 0.04; calcium, 1.12 +/- 0.04; magnesium, 1.47 +/- 0.08; and phosphate, 0.94 +/- 0.09, with a mean TF-plasma (P) inulin concentration ratio of 1.78 +/- 0.14 (n = 32). The TF/UF potassium value significantly increased in association with TF/P inulin to a mean value of 1.26 +/- 0.06. Accordingly, 29% of the filtered potassium was reabsorbed in the superficial proximal tubule compared with 43% of the filtered sodium. The loop of Henle reabsorbed 55-60% of the filtered sodium, chloride, and calcium, whereas considerably less magnesium (33%) was reabsorbed. Segments beyond the distal tubule collection site reabsorbed little of the delivered magnesium, which supports the notion that the loop of Henle is the principal segment accounting for adjustments in magnesium balance. These studies indicate that the superficial nephron of the rabbit performs similar to other species reported, except potassium reabsorption is significantly less in the proximal convoluted tubule.

Acid-Base Effects of Combined Renal Deletion of NBCe1-A and NBCe1-B

2022 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Jill W. Verlander ◽  
Gary E Shull ◽  
Autumn N. Harris ◽  
I. David Weiner
Keyword(s):  
Proximal Tubule ◽  
Splice Variant ◽  
Molecular Mechanisms ◽  
Ammonia Excretion ◽  
Basal Diet ◽  
Acid Base ◽  
Outer Medulla ◽  
Ammonia Metabolism ◽  
Induced Changes ◽  
Acid Loading

The molecular mechanisms regulating ammonia metabolism are fundamental to acid-base homeostasis. Deleting the A splice variant of the Na⁺-bicarbonate cotransporter, electrogenic, isoform 1 (NBCe1-A) partially blocks the effect of acidosis to increase urinary ammonia excretion, and this appears to involve the dysregulated expression of ammoniagenic enzymes in the proximal tubule (PT) in the cortex, but not in the outer medulla (OM). A second NBCe1 splice variant, NBCe1-B, is present throughout the PT, including the OM, where NBCe1-A is not present. The current studies determined the effects of combined renal deletion of NBCe1-A and NBCe1-B on systemic and proximal tubule ammonia metabolism. We generated NBCe1-A/B deletion using Cre-loxP techniques and used Cre-negative mice as controls. Since renal NBCe1-A and NBCe1-B expression is limited to the proximal tubule, Cre-positive mice had proximal tubule NBCe1-A/B deletion (PT-NBCe1-A/B KO). While on basal diet, PT-NBCe1-A/B KO mice had severe metabolic acidosis, yet urinary ammonia excretion was not changed significantly. PT-NBCe1-A/B KO decreased expression of phosphate-dependent glutaminase (PDG) and phospho­enol­pyruvate carboxy­kinase (PEPCK) and increased expression of glutamine synthetase (GS), an ammonia recycling enzyme, in PT in both the cortex and OM. Exogenous acid-loading increased ammonia excretion in control mice, but PT-NBCe1-A/B KO prevented any increase. PT-NBCe1-A/B KO significantly blunted acid loading-induced changes in PDG, PEPCK, and GS expression in the proximal tubule in both the cortex and OM. We conclude that NBCe1-B, at least in the presence of NBCe1-A deletion, contributes to proximal tubule ammonia metabolism in the OM and thereby to systemic acid-base regulation.

Micropuncture analysis of single-nephron function in NHE3-deficient mice

1999 ◽  
Vol 277 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
John N. Lorenz ◽  
Patrick J. Schultheis ◽  
Timothy Traynor ◽  
Gary E. Shull ◽  
Jürgen Schnermann
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Transport Processes ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Fluid Reabsorption ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Flow Pressure

The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.

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